Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice.
Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice.
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DOI：
10.3389/fgene.2018.00370
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发表时间：
2018
影响因子：
3.7
通讯作者：
Jones BC
中科院分区：
文献类型：
--
作者：
Mulligan MK;Zhao W;Dickerson M;Arends D;Prins P;Cavigelli SA;Terenina E;Mormede P;Lu L;Jones BC
我们分析了个体差异的酒精消费后，首次曝光，并在5周的自愿酒精摄入量的雌性小鼠从39 BXD重组近交系和父母在黑暗中饮酒（DID）的方法。在该范例中，将一瓶20%（v/v）酒精作为唯一的液体源提供2或4小时，从3小时开始进入黑暗循环。连续3天，小鼠接触酒精2小时，然后第4天接触4小时，中间3天不提供酒精。我们遵循这个制度5周。对于大多数菌株，2或4小时的酒精摄入量增加超过5周的时间，与一些菌株表现出大大增加的摄入量。有相当大的和遗传的遗传变异，酒精消费后，最初的早期和持续每周曝光。两种不同的定位算法被用来确定与酒精摄入量相关的QTL，只有通过这两种方法检测到的QTL被进一步考虑。在第一个4小时的曝光中，确定了染色体（Chrs）2、6和12上的多个酒精摄入量的暗示性QTL。在第4和第8个月确定了后几周持续摄入量的暗示性QTL。包括Entpd 2、Per 3和Fto在内的30个高优先级候选基因被提名为早期和持续饮酒的QTL。此外，在Chr 15上检测到一个暗示性QTL，用于在研究期间2小时酒精摄入量的变化，并且Adcy 8被鉴定为强候选基因。生物信息学分析显示，早期和持续的酒精摄入可能是由参与信号传导的基因和途径，和/或免疫和代谢功能驱动的，而与酒精经验相关的表观遗传因素和遗传因素的组合可能会驱动渐进式酒精摄入。
We profiled individual differences in alcohol consumption upon initial exposure and during 5 weeks of voluntary alcohol intake in female mice from 39 BXD recombinant inbred strains and parents using the drinking in the dark (DID) method. In this paradigm, a single bottle of 20% (v/v) alcohol was presented as the sole liquid source for 2 or 4 h starting 3 h into the dark cycle. For 3 consecutive days mice had access to alcohol for 2 h followed by a 4th day of 4 h access and 3 intervening days where alcohol was not offered. We followed this regime for 5 weeks. For most strains, 2 or 4 h alcohol intake increased over the 5-week period, with some strains demonstrating greatly increased intake. There was considerable and heritable genetic variation in alcohol consumption upon initial early and sustained weekly exposure. Two different mapping algorithms were used to identify QTLs associated with alcohol intake and only QTLs detected by both methods were considered further. Multiple suggestive QTLs for alcohol intake on chromosomes (Chrs) 2, 6, and 12 were identified for the first 4 h exposure. Suggestive QTLs for sustained intake during later weeks were identified on Chrs 4 and 8. Thirty high priority candidate genes, including Entpd2, Per3, and Fto were nominated for early and sustained alcohol intake QTLs. In addition, a suggestive QTL on Chr 15 was detected for change in 2 h alcohol intake over the duration of the study and Adcy8 was identified as a strong candidate gene. Bioinformatic analyses revealed that early and sustained alcohol intake is likely driven by genes and pathways involved in signaling, and/or immune and metabolic function, while a combination of epigenetic factors related to alcohol experience and genetic factors likely drives progressive alcohol intake.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
56.9
作者：
CLONINGER, CR
通讯作者：
CLONINGER, CR
DOI：
10.1007/978-1-4939-6427-7_4
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Mulligan MK;Mozhui K;Prins P;Williams RW
通讯作者：
Williams RW
影响因子：
3
作者：
Chen H;Sharp BM
通讯作者：
Sharp BM
DOI：
10.1111/j.1530-0277.1996.tb01063.x
发表时间：
1996-02-01
影响因子：
3.2
作者：
Gill, K;Liu, Y;Deitrich, RA
通讯作者：
Deitrich, RA